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L0301P25 - Meiosis and Gametogenesis
__TOC__ Eukaryotes *two cell types - somatic and germ cells *somatic cells: **diploid **undergo mitosis *germ cells **any biological cell that gives rise to the gametes of an organism that reproduces sexually **found in sexual reproductive organisms **only cells capable of undergoing both mitosis and meiosis Germ Cells *primordial germ cells (PCGs) are protected from somatic cell differentiation during migration by a complex combination of transcriptional and translational suppression Primordial Germ Cell Journey *most germ cell development takes place in the embryo Process in Mice #Specification #*around 6 cells express Blimp1 gene #Commitment #*after proliferation, a subset of the Blimp1 positive cells will express Stella and commit to germline #Migration #*PCGs undergo both passive and active migration to the gonads #*any that get lost - die, but may become cancerous cells #*extensive proliferation occurs #Colonisation #*PCGs colonise in the gonad and undergo sex determination #**oogonia enter meiosis but arrest at prophase I of meiosis I until puberty #**gonocytes undergo mitosis-arrest-mitosis (fill up the testes) but do not enter meiosis until puberty Process in Humans #Specification and Commitment #*little is known about the earliest stages #Migration #*fourth week: PGCs migrate from the yolk sac and into the developing embryo #*extensive proliferation occurs during journey #Colonisation: #*PCGs enter the gonads at approximately week 6-8 of gestation Human Germ Cells Female germ cells: *PGCs differentiate into oogonia, and arrest in prophase I of meiosis at Week 12 Male germ cells: *PGCs form gonocytes *at birth, these become followed by intermediate spermatogonia and prespermatogonia Disrupted Development: Tumours of the Male Germline *if mutational event occurs, gonocyte will arrest in germ cell differentiation and transformation **does not recognise any signals *do not undergo meiosis and will remain the same until it develops into a malignant growth (seminoma - male germ cell tumour) Sex Determination *bipotential gonad **formed embryonic stages of development **potential to become testis or ovary Male Development *SRY gene **located on the Y chromosome **expressed in somatic cells of the testis **switches on a cascade of genes responsible for male gonadal development **master regulator gene ***activates testosterone production from Leydig cells which drives: ****development of male genitalia ****male anatomy and physiology ****male brain and behaviour ***turns on anti-Müllerian hormone AMH ****drives regression of the female reproductive organs ****initiates male ductal system Female Development *absence of SRY gene and presence of other positive factors **female ductal system is developed **female genitalia ***results in production of estradiol and progesterone which leads the the adult female phenotype Disruptions Errors: *chromosomal aberrations *gene-level mutations *hormones and receptors *testosterone receptors mutations Effects: *affects gonadal development *development of secondary sexual characteristics and physical development Example: Swyer syndrome - 46, XY *SRY gene not functional - male genotype, female phenotype *no germ cells, no post-pubertal development, streak ovaries Meiosis Genetic Variation Crossing Over *recombination of mother and father chromosomes during meiosis ensure shuffling of alleles Independent Assortment *homologous pairs line up, cross and split randomly *chromatids splits randomly Random Fertilisation *many possibilities Non-Disjunction Events Sex Chromosomes *Turner syndrome - X *Kleinfelter syndrome - XYY Autosomal Chromosomes *most cases of aneuploidy do not survive **termination or spontaneous miscarriage *Down - trisomy 21 *Edwards - trisomy 18 *Patau - trisomy 13 Oogenesis and Spermatogenesis Common Features *all undergo: **meiosis **extensive morphological differentiation *all incapable of surviving extended periods of time if not fertilised Different Features *spermatogenesis **equivalent meiotic divisions = four equivalent spermatids *oogenesis **meiosis is asymmetrical **only one egg is formed with 3 polar bodies *maturation timing **oogenic meiosis is interrupted at one or more stages (from prenatal until puberty **spermatogenic meiosis is rapid and uninterrupted (at puberty) Spermatogenesis Sperm Path *sperm made in testis *moves through epididymis as it matures and “learns” to swim *moves through vas deferens and through glands which provide nutrients to the cell *ejaculated through ejaculatory duct and urethra Sperm Synthesis *occurs in the germinal cell in the coiled seminiferous tubules in the testis *regulated by Leydig cells - produces testosterone Sertoli Cells Functions *sex determination: express SRY *developmental: produces AMH *hormonal regulation: **Inhibin and activins - regulate FSH secretion after puberty *stem cell regulation: **GDNF - ensures self-renewal of spermatogonial stem cells *form the blood-testis barrier **prevent the immune system from detecting sperm (foreign new cells) from being destroyed Syncytium *male germ cells do not complete cytokinesis during spermatogenesis, as cytoplasmic bridges maintain connections *allows supply of all the products of a complete diploid genome (particularly genes from sex chromosomes) *not until they become mature sperm does the connection breaks and release the sperm Sperm Morphological Changes *begin as spermatogonial stem cells *flagellum develops at the centriole *golgi complex forms the acrosome **vesicle at head of the sperm containing enzymes which allow the sperm to break through the surface of the egg *flagellum develops into the tail *cytoplasm is lost *mitochondria aggregate at the mid piece **produces energy to allow swimming Oogenesis *approx 6 million oocytes at weeks 16-20 *however number decreases dramatically by birth to approx 1 million oocytes *the number decreases as the female ages Maturation #before birth: cells from ovary surround oocyte to form primordial follicle #at birth: oocytes completely enclosed in follicular (granulosa) cells #*follicular cells: secrete a meiotic inhibitory factor maintaining meiotic arrest (released from inhibition shortly before ovulation) #*oocytes: secretes factors (BMP15 and GDF9) to promote development of follicular cells #to puberty #*follicle size increases ∝ oocyte size #*increase in number of follicular cells #*additional cellular layers are formed which will form the theca interna and externa #**theca cells initially secrete an angiogenic factor, which stimulates blood vessel formation in the layer, to support growth of the follicle #as puberty approaches, follicle stimulating hormone (FSH) produced by pituitary gland acts on follicular cells to stimulate: #*low level oestrogen production #*formation of antrum (liquid filled cavity) #10-12 hours before ovulation, meiosis resumes #*in response to pituitary hormones, theca cells produce lutenising hormone (LH) #*granulosa cells produce LH receptors to respond to the LH surge #ovulation #*up to 50 follicles start the maturation process each month, however only one will dominate #*dominant follicle is defined around 7 days prior to ovulation #**enlarges, becomes FSH-independent, and secretes high levels of inhibit #**inhibin suppresses pituitary FSH production causing the remaining semi-matured follicles to degenerate - atretic follicles Gametes Sperm *compact nuclei carry few products into the egg (apart from their DNA and the centriole) Oocyte *supplies essential proteins and mRNAs the embryo needs for first few days of development until the foetal genome switches on Similarities and Differences of Gametes *PGCs; undergo a long journey to the gonad *once in the gonad, they are surrounded by: **support cells (Sertoli/granulosa) **hormone-producing cells (Leydig/theca) *they undergo significant maturation during their development *they are the only cell types in the body to undergo meiosis **produce haploid germ cells that combine to form a new person